In Vitro Antiviral Efficiency of İvermectin Against Peste des Petits Ruminants (PPR) Virus

Abstract

Peste des petits ruminants (PPR) cause significant economic losses in sheep and goat breeding and are listed as notifiable diseases by the World Animal Health Organization. Although vaccination is the most effective solution for control of PPR, there is no antiviral drug that directly affects the PPR virus (PPRV). In recent years, Ivermectin (IVM), a broad-spectrum antiparasitic, has also shown in vitro antiviral activity against several viruses. In this study, we aimed to investigate the antiviral efficiency of IVM at the stages of viral replication, cell-attachment and cell-entry of PPRV. To evaluate the efficacy of IVM at the viral-replication stage in Vero cells, the viral titers from PPRV infected cultures treated with non-cytotoxic IVM concentrations (1 and 2,5μM) were compared to titers from PPRV infected cultures without IVM by virus titration assay for 8 days. In the presence of 2,5μM IVM, the mean viral titers at the virus replication stage were significantly reduced by 1,12log10 TCID50/0,1ml (P<0,05). To evaluate the antiviral activity of IVM against PPRV at the cell-attachment and penetration stages, the virus titers of the untreated virus and virus treated with 2,5μM IVM were compared by virus titration assay on day 7 post-infection. As a result of the assays, no change in the viral titer was detected at the cell-attachment, while a decrease in viral titer of 0,37log10 TCID50/0,1ml was detected in the penetration stage. As a result of treatment of PPRV infected cells with 2,5μM IVM, the inhibition rates of infectious virions were determined to be 92,50% in the viral replication, 57,83% in the penetration and 0,00% in the cell-attachment stages. Consequently, the antiviral activity of IVM is predicted to be more effective in the late stages of the PPRV replication. This study has demonstrated that IVM can inhibit PPRV replication and may be potential drug for PPR.

Keywords

• Ivermectin
• Antiviral efficiency
• In vitro testing
• Peste des petits ruminants virus
• PPR

İvermektinin Küçük Ruminant Vebası (PPR) Virusuna Karşı İn Vitro Antiviral Etkinliği

Abstract

Küçük ruminant vebası (PPR), koyun ve keçi yetiştiriciliğinde önemli ekonomik kayıplara neden olan ve Dünya Hayvan Sağlığı Örgütü tarafından bildirimi zorunlu hastalıklar listesinde yer alan bir hastalıktır. Hastalığı kontrol altında tutmanın en etkili çözümü aşı uygulamaları olsa da, enfeksiyonun ortaya çıktığı durumlarda Küçük ruminant vebası virusuna (PPRV) doğrudan etki gösteren bir antiviral ilaç bulunmamaktadır. Nematodlara karşı uygulanan geniş spektrumlu bir antiparaziter ajan olan ivermektinin (IVM) son yıllarda çeşitli viruslara karşı in vitro antiviral aktiviteye sahip olduğu da bildirilmiştir. Bu çalışmada, PPRV’nin hücreye tutunma, giriş ve replikasyon aşamalarında IVM’in antiviral aktivitesinin değerlendirilmesi amaçlanmıştır. Vero hücrelerinde IVM’nin viral replikasyon aşamasındaki etkinliğini değerlendirmek için, IVM ile muamele edilmeyen ve non-sitotoksik IVM konsantrasyonları (1 ve 2,5 μM) ile tedavi edilen PPRV’nin viral titreleri enfeksiyon sonrası 8 gün boyunca karşılaştırıldı. 2,5 μM IVM varlığında PPRV’nin replikasyon aşamasında ortalama viral titre değerlerinde l,12 log10 DKID50/0,1ml düzeyinde düşüş ile önemli oranda azalma görüldü (P<0.05). Hücreye tutunma ve giriş aşamalarında IVM'nin PPRV’ye karşı antiviral aktivitesini değerlendirmek amacıyla, IVM ile muamele edilmeyen ve 2,5 μM IVM ile muamele edilen virusun viral titreleri, virus ekimini takiben 7. günde virus titrasyon testi aracılığıyla karşılaştırıldı. Testler sonucunda hücreye tutunma aşamasında viral titrede bir değişiklik saptanmazken, hücreye giriş (penetrasyon) aşaması testlerinde viral titre değerinde 0,37 log10 DKID50/0,1ml düzeyinde bir düşüş belirlendi. PPRV’nin 2,5 μM IVM ile muamelesi sonucunda enfeksiyöz virionların inhibisyon oranları viral replikasyon aşamasında %92,50, hücreye giriş aşamasında %57,83 ve hücreye tutunma aşamasında %0,00 olarak belirlendi. Elde edilen veriler doğrultusunda, IVM’nin antiviral etkinliğinin PPRV çoğalma siklusunun geç aşamalarında daha etkili olduğu öngörülmektedir. Bu çalışma, IVM’nin PPRV’yi inhibe edebildiğini ve IVM’nin bir anti-PPRV ilacı olma potansiyeline sahip olabileceğini göstermiştir.

Keywords

• İvermektin
• Antiviral etkinlik
• İn vitro test
• Peste des petits ruminants virus
• PPR

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